Control of regulatory T cells and T helper cells in human diseases: from bench to bedside.
Control of regulatory T cells and T helper cells in human diseases: from bench to bedside.
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DOI：
10.1093/jmcb/mjt013
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发表时间：
2013-06
影响因子：
5.5
通讯作者：
Xiaohui Zhou;Bin Li;H. Fan;Zhongmin Liu
中科院分区：
文献类型：
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作者：
Xiaohui Zhou;Bin Li;H. Fan;Zhongmin Liu
FoxP3介导的基因表达机制。纪念斯隆-凯特琳癌症中心的Alexander Rudensky团队展示了FoxP3如何与其他调节器合作，以确保Treg在基础和炎症环境中的稳定性和功能。FoxP3的合作伙伴中有很高比例是FoxP3的直接靶标，这表明FoxP3与几个序列特异性转录因子之间的表达与合作是相互调控的闭路连接。上海巴斯德研究所的李斌的研究小组发现了FoxP3+Tregs的两个负调控因子，Stub1和Dbc-1。Stub1通过促进蛋白酶体介导的FoxP3降解来负向调节Tregs抑制活性，而DBC-1是FoxP3复合体的一个重要亚单位，在炎症过程中通过caspase依赖的机制减弱FoxP3的活性。此外，纪念斯隆-凯特琳癌症中心的李明报道了一种新的依赖Foxo1的转录程序来控制Tregs细胞的功能。据本次会议报道，影响Tregs发育和功能的其他因素包括先天免疫成分C3aR/C5aR、NF-kB和Nrp1-Sema4a。
mechanism of FoxP3-mediated gene expression. Alexander Rudensky’s group from Memorial Sloan-Kettering Cancer Center showed how FoxP3 cooperated with other regulators to ensure the stability and function of Tregs in basal and inflammatory environments. A high proportion of identified partners of FoxP3 were direct targets of FoxP3, indicating a close-circuit connectivity of reciprocal regulation of expression and cooperation between FoxP3 and several sequence-specific transcription factors. Bin Li’s group from Institut Pasteur of Shanghai found two negative regulators of FoxP3 + Tregs, Stub1 and DBC-1. Stub1 negatively modulates Tregs suppressive activity by promoting proteasome-mediated degradation of FoxP3, while DBC-1 is an essential subunit of the FoxP3 complex and is responsible for attenuating FoxP3 activity by a caspase-dependent mechanism during inflammation. Furthermore, a novel Foxo1-dependent transcription program was reported to control Tregs cell function by Ming O. Li at Memorial Sloan-Kettering Cancer Center. As reported in this meeting, other factors that impinged on the Tregs development and functions included the innate immune components C3aR/C5aR, NF-kB and Nrp1-Sema4a.